From dozens of publications, it has been know that the ion traps of both ion cyclotron resonance and quadrupole high frequency ion-trap mass spectrometers should not be filled with ions beyond a certain limiting value, as otherwise the ion cloud will have a noticeable effect on the oscillation behavior of the ions being detected or ejected and detection via resonance absorption or resonance ejection will therefore cease to yield the correct mass determination.
A method of control is described in Patents U.S. Pat. No. 4,548,884 (EP 0 113 207 B1) for the general case and U.S. Pat. No. 5,107,109 (EP 0 237 268 B1) for the specific case. Both cases aim to overcome problems with the feeding of substances from gas chromatography. The patents apply to quadrupole high frequency ion-trap mass spectrometers with non-resonant ion ejection at the stability limit of the Mathieu diagram. In both cases, the xe2x80x9cnumber of ionsxe2x80x9d is controlled in the trap.
Up to now, always the xe2x80x9cnumber of ionsxe2x80x9d in the ion trap has been controlled. This is the case also for the resonant ejection of ions during the mass scan. The number of ions is being easily obtained from a preliminary measurement, a xe2x80x9cprescanxe2x80x9d (according to U.S. Pat. No. 5,107,109 or EP 0 237 268 B1) or, if spectra could be acquired rapidly enough, by integrating the ion current of one or more previous spectra, as described in U.S. Pat. No. 5,559,325 (GB 2 280 781 or DE 43 26 549).
In both cases, the xe2x80x9cnumber of ionsxe2x80x9d, or better: the total charge, is measured in the trap and used for control purposes. This xe2x80x9cnumber of ionsxe2x80x9d is determined as the integral of the ion current via a previously recorded spectrum or is determined by a preliminary experiment where the ion trap is briefly filled and then rapidly emptied while carrying out an integral measurement of the ejected ions. For this control, it is assumed that the measurement of the ion current via secondary electron multipliers is accurate enough; the dependence of the measurement on the structure and charge of the ions is neglected with complete justification since, in principle, the measurement itself is sufficient for the accuracy of the control.
However, controlling the number of ions in the ion trap has always failed to yield the optimum results. In particular, the sensitivity of the ion trap is considerably diminished due to a sufficiently large safety tolerance which has to be maintained. In many cases, the maximum number of ions which can be tolerated is by far not reached, that is, the number of ions which can be stored without worsening the quality of the spectrum. For safety reasons, it is often necessary to remain below the optimum value by a factor of three to five, thereby sacrificing valuable sensitivity.
It is very easy to observe that a spectrum which contains only a single ion species (a group of isotopes) in the lower mass range at, for example, 300 atomic mass units, tolerates a significantly larger number of ions than a spectrum with only one ion species in the upper mass range at, for example, 3000 mass units. For this reason, the usual method which has been adopted until now of simply controlling the number of ions at a fixed target value cannot be used to minimize the effects of ion filling on the quality of the spectrum while maintaining the highest level of sensitivity. In the case of heavy ions, the number of ions is too large and in the case of light ions, the number of ions is too small.
Apart from this, it can be observed that a spectrum containing only a single species of ions (of essentially one mass) tolerates significantly fewer ions than a spectrum containing many different species of ions of similar intensity but with different masses which are, to some extent, distributed reasonably evenly over the mass range of the spectrum. The distribution depends on the substance or mixture of substances which has been introduced and cannot be predicted.
These two observations, which are easily obtained, confirm that the previously used method of controlling the number of ions in the ion trap will not lead to the optimum utilization of the sensitivity of an ion trap mass spectrometer.
In accordance with the invention, a new control parameter is applied that avoids the effect of the ion load on the spectrum quality better than just the number of ions, especially for resonance ejection of ions from the ion trap. A spectrum of optimum signal strength is measured while maintaining the highest sensitivity, even if the composition of ions with respect to their mass-to-charge ratio is varied. To produce an undistorted spectrum at the optimum signal strength, control is not determined by the xe2x80x9cnumber of ionsxe2x80x9d but by a new physical parameter composed of both the charge and the mass of the ions. This parameter is called the xe2x80x9ccharge inertiaxe2x80x9d xcexc and is proportional to the charge q and the square root of the mass-to-charge ratio of the ion {square root over (m/q)}. Thus the charge inertia becomes xcexc=q{square root over (m/q)}={square root over (q/m)}. Both the actual and the target filling values in the ion trap are defined as the sum of the charge inertias of all ions in the trap. This charge inertia has a different physical dimension and a different measuring unit: while the charge has the unit Axc3x97s (Ampere second), the charge inertia has the unit (Axc3x97sxc3x97kg)xc2xd.
The invention consists of controlling the filling of the ion trap for a sequence of spectrum acquisitions so that the filling status, which is defined as the sum of charge inertias xcexc of all ions in the ion trap, assumes a predetermined target value for the charge inertia as near as possible each time the trap is filled. At the same time, the target value is chosen to be slightly below the threshold above which the effect of the ions in the ion trap on the spectrum can be seen and measured by a slight displacement (slightly delayed ejection) and slight broadening (slightly smeared ejection) of the mass lines. Control can be achieved by automatically comparing the actual measured value of the filling status in prior spectra with the target value and then choose a correspondingly longer or shorter filling time for the next spectrum.
The actual value of the filling status for a previously recorded spectrum can be obtained, for example, by weighted summation of the measured ion current values using the square root of the mass-to-charge ratio as the weighting factor. The prevailing ion current can be multiplied by the square root of the mass-to-charge ratio on both a digital and an analog basis, for example, in an analog way by increasing the amplification of the ion current signal amplifier proportional to the square root of the mass-to-charge ratio while the spectrum is being recorded and feeding the amplifier output to an integrator. The summation for determining the measured actual filling status can be obtained in real time while the spectrum is being recorded so that the actual value is immediately available after the spectrum has been scanned. The filling rate for the next spectrum can then be calculated from the actual filling status, that is from the charge inertia calculated by the spectrum and the known filling time. This filling rate is then used for controlling ion filling for the next spectrum.
The trend of a filling rate which may rapidly change from one spectrum to the next (due to the rapidly changing concentration of substances fed to the mass spectrometer from, for example, a chromatograph) can be calculated by calculating the trend of filling rates from several previously recorded spectra, as shown by the description of the trend calculation in U.S. Pat. No. 5,559,325 (GB 2 280 781, DE 43 26 549). The trend calculation produces a prospective filling rate which is then used for control.
It now appears that the optimum filling of an ion trap for producing a high quality mass spectrum is determined by the distribution of the ions over the individual sections of the spectrum. If the ions are concentrated within a small mass-to-charge range, filling must be maintained at a much lower status than if the ions are distributed uniformly over the entire spectrum.
Another basic idea in this invention therefore takes into account the effect of ion clustering within narrow ranges of specific masses (that is mass-to-charge ranges) during control by adapting the target value for the filling status. Also in this case information about ion clustering is obtained from previously recorded spectra.
In order to achieve this, the maximum charge inertia which appears within a small specific mass range (for example, within a m/z range of 5, 10, 20 or 50 atomic mass units divided by the number z of elementary charges) is compared with the total charge inertia for the entire spectrum. If the quotient of the total charge inertia and the maximum charge inertia in the range is almost equal to unity, then all the ions in the spectrum are clustered within this small mass range and the target value for control will have to be given a correspondingly low value. However, if the maximum charge inertia of the individual mass ranges is small in comparison to the total charge inertia, then the target value for the control can be higher. A good proportionality factor to use for the target value is, for example, the square root of the quotient of the total charge inertia and the maximum charge inertia found within the mass ranges. However, other relationships can also be used. Fixed mass-to-charge ranges can be used to establish the maximum for the charge inertia, but these can also be shifted over the entire spectrum in a similar way to a xe2x80x9crunningxe2x80x9d average.